Chronic inflammation associated with cigarette smoke fosters malignant transformation and tumor cell proliferation and promotes certain nonneoplastic pulmonary diseases. The question arises as to whether chronic inflammation and-or colonization of the airway can be attributed, at least in part, to tobacco-associated microbes bacteria, fungi, and spores and-or microbial toxins endotoxins and mycotoxins in tobacco. To address this question, a literature search of documents in various databases was performed. The databases included PubMed, Legacy Tobacco Documents Library, and US Patents. This investigation documents that tobacco companies have identified and quantified bacteria, fungi, and microbial toxins at harvest, throughout fermentation, and during storage. Also characterized was the microbial flora of diverse smoking and smokeless tobacco articles. Evidence-based health concerns expressed in investigations of microbes and microbial toxins in cigarettes, cigarette smoke, and smokeless tobacco products are reasonable; they warrant review by regulatory authorities and, if necessary, additional investigation to address scientific gaps.